Anita T. Shaffer
Any lingering skepticism about immunotherapy as an anticancer strategy appears to have been banished by research presented at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting, with fresh data from several key trials translating into excitement in clinical circles and in the investment arena.
The most promising results came from an emerging class of antibodies that target the programmed death-1 (PD-1) pathway to take the brakes off the patient’s immune system, employing the same type of “checkpoint blockade” approach that ipilimumab (Yervoy) pioneered in metastatic melanoma.
With the monoclonal antibody nivolumab leading the field, the PD-1 pathway agents have been most effective in melanoma, but also are making an impact in non-small cell lung cancer and renal cell carcinoma. Some researchers are calling it a “breakthrough strategy.”
Yet researchers and pharmaceutical industry analysts say the excitement over immunotherapy extends to other strategies under investigation, which include vaccines and gene therapies, although perhaps with not as much enthusiasm as the checkpoint blockers have generated.
For longtime believers in the potential for immunotherapy, it is a time for celebration.
James P. Allison, PhD
“There is a great sense of gratification because for many, many years I’ve had the conviction that despite what seemed to be frustrations, there was a way of getting it to work if we just studied mechanisms enough,” said James P. Allison, PhD, whose research led to the FDA’s approval of ipilimumab in 2011, in an interview. “I think that these advances show that it really can work, and I think offer a great opportunity for saving a lot of lives.”
Allison, who is professor and chair of The University of Texas MD Anderson Cancer Center Department of Immunology, is particularly enthusiastic about the prospect of combining checkpoint blockers with each other and using these agents sequentially or in combination with targeted therapies.
He noted the results of phase I research presented at ASCO in which nivolumab was combined with ipilimumab, which blocks CTLA-4, leading to deep tumor regression in approximately one-third of patients with nonresectable stage III or IV melanoma.1
Allison said the field of immunotherapy needs to move forward, not only in the area of combination checkpoint blockers but also in the discovery of reagents that target other regulatory molecules on T-cells. When such inquiries are joined with the fields of genomics and targeted therapies, “then I think that we are going to see some real, real progress and very rapidly,” he said.
Jedd D. Wolchok, MD, PhD
Jedd D. Wolchok, MD, PhD, a medical oncologist at Memorial Sloan-Kettering Cancer Center in New York City who presented the nivolumab/ipilimumab combination research, is similarly optimistic.
“For those of us who have been investigating means to use the immune system to treat cancer for decades, this is a glorious time,” said Wolchok. “We now have multiple medicines which are very precisely designed to interact with different on and off systems that the immune system uses to control T cells and antibodies. We’re now seeing the benefits with significant numbers of patients having very durable regressions.”
Many Therapies Under Study
More than 30 clinical trials involving nearly as many immunotherapy agents have reached the phase III stage, according to the Cancer Research Institute, a New York City nonprofit that provides funding to scientists in the field.
Many of these trials are evaluating ipilimumab in various settings. In melanoma, these include separate studies that compare treatment with and without ipilimumab in combinations with interferon alfa-2b, dacarbazine, or nivolumab. Other studies are looking at ipilimumab in combination with etoposide and platinum therapy versus those two drugs alone in small cell lung cancer, and at adding ipilimumab to paclitaxel and carboplatin versus that standard in squamous, non-small cell lung cancer. Ipilimumab also is under investigation versus placebo in separate clinical trials for patients with castration-resistant prostate cancer.